Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin

Cell. 2003 Mar 7;112(5):725-36. doi: 10.1016/s0092-8674(03)00123-5.


Boundary elements hinder the spread of heterochromatin, yet these sites do not fully account for the preservation of adjacent euchromatin. Histone variant H2A.Z (Htz1 in yeast) replaces conventional H2A in many nucleosomes. Microarray analysis revealed that HTZ1-activated genes cluster near telomeres. The reduced expression of most of these genes in htz1Delta cells was reversed by the deletion of SIR2 (sir2Delta) suggesting that H2A.Z antagonizes telomeric silencing. Other Htz1-activated genes flank the silent HMR mating-type locus. Their requirement for Htz1 can be bypassed by sir2Delta or by a deletion encompassing the silencing nucleation sites in HMR. In htz1Delta cells, Sir2 and Sir3 spread into flanking euchromatic regions, producing changes in histone H4 acetylation and H3 4-methylation indicative of ectopic heterochromatin formation. Htz1 is enriched in these euchromatic regions and acts synergistically with a boundary element to prevent the spread of heterochromatin. Thus, euchromatin and heterochromatin each contains components that antagonize switching to the opposite chromatin state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / genetics*
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Euchromatin / genetics*
  • Euchromatin / metabolism
  • Eukaryotic Cells / metabolism*
  • Evolution, Molecular
  • Gene Deletion
  • Gene Expression Regulation, Fungal / genetics
  • Gene Silencing / physiology*
  • Heterochromatin / genetics*
  • Heterochromatin / metabolism
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Histones / genetics*
  • Histones / metabolism
  • Insulator Elements / genetics
  • Mutagenesis, Insertional / genetics
  • Oligonucleotide Array Sequence Analysis
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
  • Sirtuin 2
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Telomere / genetics
  • Telomere / metabolism


  • Euchromatin
  • Heterochromatin
  • Histones
  • SIR3 protein, S cerevisiae
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • histone H2A.F-Z
  • SIR2 protein, S cerevisiae
  • Sirtuin 2
  • Sirtuins
  • Histone Deacetylases